Mixed Results for Alzheimer's Cocktail Again

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Note that in this randomized, controlled, double-blind trial, one measure of improved memory performance was seen in drug-naÃ¯ve patients with mild Alzheimer's disease with a liquid nutrient product.

A new clinical trial of a liquid nutrient cocktail billed as improving cognition in Alzheimer's disease again yielded mixed results, bettering placebo on a few measures but not on many others.

Patients assigned to the drink, called Souvenaid, in a randomized, 24-week, manufacturer-funded trial showed significant improvement in one interpretation of memory function scores on the Neuropsychological Test Battery (NTB) relative to placebo, the study's primary endpoint, according to Philip Scheltens, MD, of VU University Medical Center in Amsterdam, and colleagues.

Changes in brain electrical activity also suggested increases in functional connectivity between brain regions, Scheltens and colleagues indicated in the July issue of the Journal of Alzheimer's Disease.

But on a host of secondary measures of cognition -- the Rey Auditory Verbal Learning Test, the cognitive subscale of the Alzheimer's Disease Assessment Scale, the Letter Digit Substitution Test, and the the Wechsler Memory Scale -- patients drinking the cocktail did not fare any better than those assigned to placebo, the researchers reported.

Developed by Richard Wurtman, MD, of the Massachusetts Institute of Technology in Cambridge, Mass., the cocktail includes omega-3 fatty acids, uridine, choline, selenium, folic acid, and vitamins B6, B12, C, and E.

Research by Wurtman and others suggested that these nutrients would promote formation of new nerve synapses, thereby countering the neurodegeneration that underlies Alzheimer's disease and other forms of dementia.

In the current study, Scheltens and colleagues randomized 259 patients with mild Alzheimer's disease to 125 mL of Souvenaid or a placebo drink on a double-blind basis. Participants took the drink once daily.

The minimum score on the Mini-Mental State Examination for inclusion in the study was 20 (mean 25).

On the primary outcome measure, the NTB memory domain z-score, the mean 24-week change from baseline with the nutrient drink did not differ significantly from placebo (+0.202 for Souvenaid versus +0.111 for placebo, P=0.090).

But an analysis of the "trajectory" of changes over the 24-week period revealed a significant advantage for Souvenaid (P=0.023), the researchers asserted.

This was because, during the final 12 weeks of the study, patients on placebo showed a worsening in mean NTB memory domain scores after improving during the first 12 weeks, whereas Souvenaid patients showed continued improvement throughout the study period.

There was no difference between groups in NTB executive function domain scores.

Scheltens and colleagues conducted electroencephalography studies in 86 of the Souvenaid patients and 93 from the placebo group.

Functional connectivity analysis in the delta band "revealed a significant difference in trajectory over 24 weeks between study groups in favor of the active group," they wrote, adding that the effect was not evident in other frequency bands.

Adverse events were similar in the two groups and, in most cases, were considered unrelated to the drinks.

"Our results warrant further investigation of the clinical potential of Souvenaid in preclinical or clinical conditions characterised by synaptic loss, in particular Alzheimer's disease," the researchers concluded.

Despite their enthusiasm, the results seemed unlikely to win over critics of the group's first trial, who had pointed out -- as was the case in the new study -- that Souvenaid did not outperform placebo on most measures.

Moreover, although the new report indicated that efficacy outcomes were analyzed on an intent-to-treat basis, Scheltens and colleagues did not say what outcomes were imputed to the study's 21 dropouts. Also, data on a total of 28 participants were omitted without explanation from the primary endpoint analysis of 24-week NTB memory score outcomes.

Limitations cited by Scheltens and colleagues included reliance on clinical examination for the Alzheimer's disease diagnoses, the modest sample size, and the short study duration.

The study was funded by Nutricia, a unit of Group Danone, which makes Souvenaid.

Several co-authors reported consulting or advisory relationships with Nutricia. Four others were employees of Nutricia or Danone.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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